In the project we are using our three-dimensional structure of the thyroid hormone receptor to design mutations which enable us to test selective functions of the receptor. The thyroid hormone receptor is now known to be a multifunctional protein, although the mechanisms of its various actions are not defined. By using the structure as a guide we are now able to create mutations which easily lead to loss of individual functions, with no effect on other functions. We introduced mutations into the chicken thyroid hormone receptor alpha and the human thyroid hormone receptor be ta. We succeeded in defining the region of the hormone binding domain which is involved in binding to the coactivator protein GRIP1 (glucocorticoid receptor interacting protein The graphics facilities at the Computer Graphics Laboratory are of critical importance to our work in this area.